FSH receptor genotype is associated with pregnancy but not with ovarian response in IVF

Two very common single nucleotide polymorphisms at positions 307 and 680 in exon 10 of the FSH receptor gene have been associated with ovarian response in IVF. This observational study evaluated the role of the FSH receptor genotype in the prediction of poor response and clinical pregnancy in IVF in comparison with other markers, such as age, basal FSH, anti-Müllerian hormone and antral follicle count. In addition, the in-vitro cAMP response towards recombinant FSH in cultured granulosa cells of patients with different FSH receptor genotypes was determined. A total of 105 IVF patients undergoing ovarian stimulation in a long suppression protocol were included in the study. The ovarian response was comparable between patients with different FSH receptor genotypes. Patients with polymorphism Ser/Ser had implantation and pregnancy rates that were three times higher compared with patients with polymorphism Asn/Asn. FSH receptor genotype was not associated with a poor response in IVF, but showed a positive association with pregnancy, independent of age. There was no difference in cAMP production in cultured granulosa cells of patients with different FSH receptor genotypes (n=62). It is concluded that FSH receptor genotype is associated with pregnancy in IVF, but not with ovarian response.     

The effect of danazol on anterior pituitary function.

Danazol was given in a daily dose of 600 mg for 15 days to five postmenopausal women and five normal adult men. The basal levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), prolactin (PRL), and cortisol were determined for 3 days before treatment and during the last 3 days of treatment. A combined intravenous injection of 25 micrograms of gonadotropin-releasing hormone (GnRH) and 200 micrograms of thyrotropin-releasing hormone (TRH) was also given before and on the last day of treatment to each subject. Danazol reduces basal levels of FSH and LH and their cumulative response to GnRH but exercises no significant effect on either basal levels of TSH or PRL or their response to TRH, nor does it modify basal cortisol secretion.     

Follicle-stimulating hormone--regulated granulosa cell steroidogenesis: involvement of the calcium-calmodulin system

The role of the calcium-calmodulin system in the gonadotropic regulation of ovarian steroidogenesis was studied by investigating the influence of various agents known to alter calcium metabolism or calmodulin activity on basal and follicle-stimulating hormone (FSH)-stimulated production of progesterone by rat granulosa cells in vitro. Lanthanum, a specific calcium antagonist, attenuated FSH-stimulated cyclic adenosine monophosphate (cyclic AMP) and progesterone production. [Ethylene-bis(oxyethylene-nitrilo)]tetraacetic acid (EGTA) significantly reduced this steroidogenic response but failed to alter the synthesis of the nucleotide. Although progesterone production was markedly increased by dibutyryl cyclic AMP, this was significantly lowered by an inhibitor of calcium uptake, verapamil. FSH-stimulated production of cyclic AMP and progesterone and dibutyryl cyclic AMP-induced progesterone biosynthesis were all significantly reduced by trifluoperazine, a specific inhibitor of calmodulin. These results indicate the existence of at least two sites in the trophic regulation of granulosa cell steroidogenesis which are calcium- and calmodulin-dependent: one localized at the level of cyclic AMP production, and the second at an unidentified step(s) distal to the formation of this nucleotide.     

Influence of Danazol on gonadotropin secretion and synthesis by rat pituitary cells in cultures. Comparison with gonadal steroids

Increasing concentrations of estradiol, testosterone, progesterone (1.10(-10) to 1.10(-7] and Danazol (1.10(-9) to 1.10(-6) M) have been added to male rat pituitary cells maintained in monolayer cultures for a preincubation period of three days followed by a six hour incubation with or without GnRH (1.10(-8) M). Concentrations of LH and FSH have been assessed in the culture media and in the cells at the end of the experiments allowing an estimation of the influence of these steroids on gonadotropin release and synthesis. In these experimental conditions, estradiol does not modify basal and GnRH induced FSH release and synthesis but reduces the GnRH-induced response of LH. Testosterone and progesterone stimulate synthesis of FSH but inhibit synthesis and secretion of LH in the presence of GnRH. These results have been compared with those of literature. Danazol, in the same experimental conditions, stimulates synthesis of gonadotropins and simultaneously inhibits their release induced by the presence of GnRH. We conclude that Danazol is able to act at the pituitary level as testosterone which is in good agreement with its androgenic properties.     

Follicle-stimulating hormone bioactivity in idiopathic normogonadotropic oligoasthenozoospermia: double-blind trial with gonadotropin-releasing hormone.

OBJECTIVE: To identify, among patients with idiopathic normogonadotropic oligoasthenozoospermia, those with low bioactive follicle-stimulating hormone (FSH), possibly because of inadequate gonadotropin-releasing hormone (GnRH) pulsatility, whose bioactive FSH and sperm could be improved by GnRH treatment. DESIGN: Randomized, double-blind, placebo-controlled trial with intranasal (IN) GnRH, followed by open GnRH treatment. SETTING: Outpatient endocrinology clinic. PATIENTS: Twenty-eight infertile men with idiopathic normogonadotropic oligoasthenozoospermia. INTERVENTIONS: Gonadotropin-releasing hormone or placebo was self-administered IN every 2 hours. MAIN OUTCOME MEASURES: Serum immunoreactive and bioactive FSH and semen analyses. RESULTS: Ten men showed a low basal FSH bioactive/immunoreactive ratio, which increased in 5 of them under GnRH without parallel sperm modification. Sperm improvements were observed in 10 patients with no parallel evolution of FSH bioactive/immunoreactive ratio. Unpredicted by sperm changes, three pregnancies developed on placebo and 5 on GnRH. CONCLUSIONS: Low bioactive FSH was not the cause of idiopathic normogonadotropic oligoasthenozoospermia in our patients and could not predict response to GnRH. Pulsatile GnRH did not improve sperm beyond random fluctuations.     

Human granulosa cell tumor: stimulation of steroidogenesis by gonadotropins in vitro.

A 59-year-old previously oophorectomized woman underwent surgery for a recurrent malignant granulosa cell tumor. Specimens and dispersed cells from the tumor tissue were incubated for 2 hr and cultured for 48 hr, respectively, with and without gonadotropins. Steroids and cyclic AMP (cAMP) concentrations were measured in the incubation and culture media. Incubated specimens from the tumor tissue released measurable amounts of cAMP, progesterone, and estradiol into the medium. Human follicle-stimulating hormone (FSH) 1 microgram/ml significantly stimulated the formation of cAMP and both steroids. Human luteinizing hormone (LH) 1 microgram/ml stimulated cAMP and progesterone but not estradiol release. Human chorionic gonadotropin (hCG) 10 micrograms/ml stimulated cAMP and progesterone formation in tumor tissue but was totally devoid of effect on estradiol release. In the tissue culture experiments progesterone and estradiol were formed in considerable amounts, with a higher capacity for progesterone than for estradiol. Progesterone formation was stimulated by FSH and hCG, while estradiol release was stimulated only by hCG. The addition of testosterone significantly enhanced estradiol formation in both incubation and culture experiments. It is concluded that the steroidogenesis of this granulosa cell tumor is sensitive to gonadotropins.     

Regulation of steroid hormone synthesis by human corpora lutea: failure of follicle-stimulating hormone to support steroidogenesis in vivo and in vitro

The authors studied the role of follicle-stimulating hormone (FSH) in luteal steroidogenesis by replacing gonadotropin-releasing hormone (GnRH) infusion with pure FSH 48 hours after ovulation in two hypogonadotropic patients. Plasma progesterone (P) and estradiol (E2) decreased after FSH administration. Human luteal cells were cultured for 48 hours in the presence and absence of FSH, human chorionic gonadotropin (hCG), testosterone (T), or dibutyryl cyclic adenosine monophosphate (Bu2cAMP). In the presence of T, E2 synthesis increased significantly, indicating an active aromatase system in these cells. Human chorionic gonadotropin as well as Bu2cAMP significantly increased E2, T, and P synthesis. Follicle-stimulating hormone did not stimulate luteal E2, T, or P synthesis. The authors conclude that FSH does not sustain luteal steroidogenesis. Moreover, the in vitro findings reveal that hCG modulation of luteal E2 synthesis is mediated principally by an increase in androgen precursors. These in vivo and in vitro results confirm a crucial role for luteinizing hormone (LH) in the maintenance of luteal steroidogenesis.     

Regulation of human prolactin secretion by gonadotropin-releasing hormone in vitro

The regulation of human prolactin (PRL) secretion by gonadotropin-releasing hormone (GnRH) was evaluated with human pituitary monolayer cell cultures. Synthetic GnRH stimulated PRL secretion when exposed to cells in an estrogen-depleted environment. This response was inhibited by pretreatment of the cells with 17 beta-estradiol (E2). A 10(-5) M GnRH antagonist inhibited luteinizing hormone (LH) but not PRL secretion when cells were maintained in an estrogen-depleted environment. However, the GnRH antagonist inhibited basal PRL secretion when cells were maintained in medium containing 10(-8) M E2. The 10(-5) M GnRH antagonist, when coincubated with 10(-5) M GnRH inhibited the release of PRL in an estrogen-depleted environment. However, coincubation of the 10(-5) M GnRH antagonist with 10(-5) M thyrotropin-releasing hormone (TRH) failed to inhibit PRL secretion. Incubation of 10(-8) M TRH and 10(-8) M GnRH produced a synergistic release of PRL in an estrogen-depleted environment. These observations led us to conclude that GnRH stimulates PRL secretion by direct action on human pituitary cells and that GnRH acts either via the gonadotrope or through receptors on the galactotrope other than that acted upon by TRH to release PRL.     

Characterizing pituitary response to a gonadotropin-releasing hormone (GnRH) antagonist in monkeys: tonic follicle-stimulating hormone/luteinizing hormone secretion versus acute GnRH challenge tests before, during, and after treatment

Pituitary sensitivity to a gonadotropin-releasing hormone (GnRH) challenge test before, during, and after GnRH antagonist administration was compared in four ovariectomized female monkeys receiving GnRH antagonist intramuscularly (IM) at increasing doses of 0.3, 1.0, and 3.0 mg/kg/day over 9 days. Three days before and 3 days after treatment, monkeys received vehicle alone. On experiment days 4, 7, 10, 13, and 16, 100 micrograms of GnRH was administered intravenously (IV) and blood drawn at 0 and 30 minutes. Before treatment, tonic follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were 248 +/- 105 and 178 +/- 31 ng/ml, respectively; after 0.3 mg/kg/day of GnRH antagonist, FSH and LH decreased to 30 +/- 6 and 41 +/- 4 ng/ml, respectively. After treatment with either 1 mg/kg/day or 3 mg/kg/day of GnRH antagonist, both gonadotropins were undetectable in serum. Monkeys with lower initial levels of gonadotropins were suppressed by 48 hours after GnRH antagonist, while those with higher tonic gonadotropins were suppressed 6 days later (FSH: r = 0.992; LH: r = 0.833). The data show that initial physiologic status is predictive of the rapidity of the suppression response induced by a GnRH antagonist and that, after achieving pituitary suppression, responsivity to an IV GnRH challenge test may be restored before normal tonic FSH/LH secretion is regained.     

The effect of varying prolactin levels on pituitary luteinizing hormone and follicle-stimulating hormone response to gonadotropin-releasing hormone.

Seventy-one women with menstrual irregularities were investigated by measurement of basal plasma estradiol, prolactin, and gonadotropin levels. They were each given an intravenous injection of 100 microgram of gonadotropin-releasing hormone (GnRH), and both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured for two hours. The women were divided into three groups on the basis of the prolactin levels: "normal," "mild elevation," and "severe elevation." For each prolactin group there was no difference in age or estradiol or basal LH and FSH levels. The pituitary response to the GnRH injection was also similar for the three groups. These data suggest that elevated prolactin levels do not interfere with pituitary gonadotropin cell function.     

Comparison of the effects of contraceptive steroid formulations containing two doses of estrogen on pituitary function.

A pituitary stimulation test with gonadotropin-releasing hormone (GnRH) and thyrotropin-releasing hormone (TRH) was undertaken to determine (1) whether pituitary responses to GnRH vary in individual women taking oral contraceptive steroids over time, (2) whether a less suppressive pituitary gonadotropin effect is produced by formulations containing less than 50 microgram of estrogen, and (3) to obtain more information concerning prolactin secretion in users of oral contraceptive steroids. The same subjects who had had a suppressed luteinizing hormone (LH) and follicle-stimulating hormone (FSH) response 6 to 9 months previously also had a suppressed response, indicating that this effect persists over time. Contraceptive formulations containing less than 50 microgram of estrogen have a lesser suppressive effect on LH release than do formulations containing 50 microgram of estrogen or more. The basal prolactin (PRL) response as well as the maximal PRL response to TRH were found to be significantly greater in subjects using oral contraceptives than in the control subjects. However, no difference in PRL response was found between the subjects using low or high doses of estrogen fomulations.     

Effect of the gonadotropin-releasing hormone antagonist ganirelix on cyclic adenosine monophosphate accumulation of human granulosa-lutein cells

OBJECTIVE: To evaluate whether the GnRH antagonist ganirelix exerts an effect on cyclic adenosine monophosphate (cAMP) production of human granulosa-lutein (GL) cells in vitro. DESIGN: In vitro cell culture study. SETTING: Research laboratory of a university hospital. PATIENT(S): Mural GL and cumulus cells were obtained from 15 patients on whom controlled ovarian hyperstimulation was being performed for intracytoplasmic sperm injection treatment. INTERVENTION(S): Mural GL and cumulus cells were cultured for 48 hours with and without 1 nM ganirelix or triptorelin. For the last 6 hours, the cells were either exposed to 1-5 IU hCG or left unstimulated. MAIN OUTCOME MEASURE(S): At the end of the culturing period, the intracellular and extracellular cAMP accumulations were measured by an (125)I-scintillation proximity assay. RESULT(S): hCG induced dose-dependent increases in total cAMP accumulation. Stimulation with 1 IU/mL hCG resulted in 9-fold and 13-fold increases, and 5 IU/mL hCG resulted in 19-fold and 14-fold increases in total cAMP release from cumulus and mural GL cells, respectively. On the other hand, treatments with 1 nM GnRH antagonist ganirelix and 1 nM GnRH agonist triptorelin did not exert any significant changes on the basal and hCG-stimulated cAMP accumulation of mural GL cells and cumulus cells as compared with controls. CONCLUSION(S): Ganirelix does not influence basal and hCG-stimulated cAMP accumulation of human GL cells in vitro. cAMP is apparently not involved in the mechanism of action of GnRH analogs in human ovary.     

Pituitary gonadotropin responsiveness to repeated gonadotropin releasing hormone (GnRH) stimulations in patients with chronic anovulation.

To evaluate whether repeated gonadotropin releasing hormone (GnRH) stimulations were superior to single GnRH administrations for the accurate assessment of pituitary gonadotropin responsiveness, the GnRH-stimulated luteinizing hormone (LH) and follicle stimulating hormone (FSH) responses of 49 hyperandrogenic patients (HA) were compared with those of 20 hypogonadotropic patients (HH) and of 24 normally cycling women (N). Blood samples were obtained at frequent intervals during GnRH administrations (25 micrograms twice within 2 h). Unstimulated LH concentrations were higher (p less than 0.001) in HA than in N and HH women. However, basal FSH levels differed only in HA from HH women (p less than 0.001). Following either GnRH stimulation, increased (p less than 0.01) LH and FSH releases were noted in all N, HA and HH women. The GnRH-stimulated LH and FSH responses to either GnRH injections were highest (p less than 0.01) in HA and lowest (p less than 0.01 vs. N) in HH women. The net LH and FSH increases over unstimulated concentrations (delta LH or FSH) in response to either GnRH stimulation were highest (p less than 0.01 or less) in HA women. By contrast, no differences were determined in the delta LH and FSH levels between the first and second GnRH stimulations within each group. These observations document different unstimulated and stimulated gonadotropin concentrations in normal cycling and anovulatory women. Gonadotropin responses to single GnRH administrations differ for anovulatory patients. Since the gonadotropin responses to the second GnRH stimulation are comparable to those during the first GnRH injections, repeated GnRH stimulations may not help to distinguish the degree of pituitary responsiveness in ovulatory from anovulatory women.     

Effect of cranial irradiation on hypothalamus-pituitary function: follow-up study one year after radiotherapy.

Hypothalamic pituitary functions were studied in 24 patients before, 6 months after and 1 year after cranial irradiation with or without radiosensitizing chemotherapy for nasopharyngeal carcinoma (NPC). The estimated average total dose was 5,000 cGy to the hypothalamus and pituitary gland. The radiosensitizing chemotherapy used was endoxan, 4,900 +/- 873 mg (mean +/- SD) and/or methotrexate, 113 +/- 30 mg. All patients had normal pituitary function before radiotherapy. There was a progressive increase in baseline serum thyrotropin (TSH) after radiotherapy. The basal serum follicle stimulating hormone (FSH) was significantly increased 6 months after radiotherapy and remained so at 1 year after radiotherapy. The TSH response to thyrotropin-releasing hormone (TRH) also progressively increased after radiotherapy, suggesting primary hypothyroidism due to neck irradiation. The peak serum TSH response to TRH became delayed after radiotherapy, suggesting a defect in TRH release. In male patients who did not receive chemotherapy, the LH response to luteinizing hormone-releasing hormone (LHRH) decreased after radiotherapy. After an initial rise in the FSH response to LHRH 6 months after radiotherapy, there was a reduction in the FSH response at 1 year. This suggests a defect in LHRH pulsatile release. However, in male patients who received radiosensitizing chemotherapy, both the FSH and LH responses to LHRH had declined at 1 year after radiotherapy, as compared with their responses at 6 months. However, these were still higher than those obtained before radiotherapy. This suggests further GnRH neuron damage, which was previously masked by chemotherapy-induced primary hypogonadism. The adrenocorticotropic hormone (ACTH) response to ovine corticotropin-releasing hormone (CRH) had not changed further at 1 year after radiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Marked suppression of gonadotropins and testosterone by an antagonist analog of gonadotropin-releasing hormone in men

To study the dose response characteristics of a gonadotropin-releasing hormone (GnRH) antagonist ([Ac-D2-Nal1,D4-Cl-Phe2,D3-Pal3,Arg5,dGlu6 (AA), d-Ala10] GnRH; Nal-Glu), 1.5 or 5.0 mg of Nal-Glu were administered to two groups of five normal men by daily subcutaneous injection for 21 days. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) were determined on multiple occasions before, during, and after the antagonist treatment. Five milligrams Nal-Glu markedly suppressed mean serum immunoreactive LH to a mean of 1.5 +/- 0.4 IU/L (+/- SEM), immunoreactive FSH to the limit of assay detection (1 IU/L), and lowered basal mean serum T to castrate range (less than 2 nmol/L). Serum bioactive LH levels also showed a marked decrease in the 5.0-mg group similar to that seen in immunoreactive LH levels. Amplitude of immunoreactive LH pulses was markedly reduced in the 5.0-mg group on day 21. A 1.5-mg dose of Nal-Glu transiently suppressed serum immunoreactive LH levels on day 1. There was a subsequent escape on the rest of the days sampled. Serum immunoreactive FSH levels were not significantly changed over the 21-day treatment period. Serum T levels were transiently suppressed only on day 1 paralleling immunoreactive LH suppression. No adverse systemic side effects occurred. Thus, the 5.0-mg dose of this GnRH antagonist provides a pharmacological means of markedly suppressing the hypothalamic-pituitary-gonadal axis and, therefore, has potential as a male contraceptive.     

Effects of clomiphene citrate on pituitary luteinizing hormone and follicle-stimulating hormone release in women before and after treatment with ethinyl estradiol.

OBJECTIVE: To evaluate the effects of clomiphene citrate (CC) on pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in hypoestrogenic women and in the same women after treatment with ethinyl estradiol (EE2). DESIGN: The study was of a prospective nature and was conducted on selected patients. SETTING: Volunteer women were studied in a tertiary care public hospital. PATIENTS: The 10 patients studied were selected on the basis of hypogonadal status (menopause, premature ovarian failure, or gonadal dysgenesis and Turner phenotype) and no hormonal treatment. INTERVENTIONS: Gonadotropin-releasing hormone (GnRH) was continually infused at the dose of 0.2 micrograms/min for 4 hours before and after the use of CC and/or EE2. MAIN OUTCOME MEASURE: The study was performed with the objective of determining the effect of estrogen (E) levels on the action of CC on in vivo gonadotropin release. RESULTS: In the presence of hypoestrogenic conditions, CC had no pituitary action. However, after EE2 treatment CC promoted greater FSH release and a significant inhibition of LH release from the pituitary. CONCLUSION: Clomiphene citrate needs a basal E level to be able to act on the pituitary. In normoestrogenic states and under GnRH stimulation, CC preferentially promotes FSH release while presenting a predominantly inhibitory effect on LH release.     

The value of basal and/or stimulated serum gonadotropin levels in prediction of stimulation response and in vitro fertilization outcome

The purpose of this study was to determine whether basal or stimulated (or both) serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on day 3 of the cycle before administration of exogenous gonadotropins can predict stimulation response and in vitro fertilization (IVF) outcome. Eighty consecutive new patients underwent a gonadotropin-releasing hormone (GnRH) stimulation test on the morning of cycle day 3. All patients underwent the same stimulation protocol consisting of a combination of FSH and human menopausal gonadotropin (hMG). Paired discriminant analysis of FSH0 (at 0 minutes from GnRH injection) and LH0 revealed seven distinct groups of patients with statistically significant differences among the means: groups 1, 2, and 3 (26.25%) with higher means FSH0:LH0; group 4 (40%) with mean FSH0:LH0 (both levels less than 10 mIU/ml) of 1:1, and groups 5, 6, and 7 (33.75%) with higher mean LH0:FSH0. Canonical discriminant analysis of both basal and stimulated serum FSH and LH levels confirmed the seven groups and did not add to the information from analysis of FSH0 and LH0 only. Serum estradiol (E2) response during stimulation, as well as the number of preovulatory oocytes aspirated and transferred, was highest in the groups with a higher mean LH0:FSH0, intermediate in the group with mean FSH0:LH0 of 1:1, and lowest in the group with a higher mean FSH0:LH0. No pregnancy occurred in the higher FSH:LH groups. It is concluded that basal serum gonadotropin levels can distinguish different populations of IVF patients who tend to behave differently in terms of E2 response, oocytes obtained and transferred, and pregnancy rates and outcome.     

Effect of ethinyl estradiol sulfonate/norethisterone acetate on gonadotropin secretion in pubertal girls

In 13 healthy tall girls the influence of the hormonal treatment with depotestrogen ethinylestradiolsulfonate and norethisterone acetate on basal and GnRH stimulated gonadotropin secretion was investigated. The investigation were performed before treatment, during the 8th to 11th cycles of treatment, and in the 4th month after finishing the therapy. LH and FSH serum levels were determined by RIA. Under treatment a suppression both of basal gonadotropin serum levels and of the stimulated LH secretion results. After treatment the mean basal gonadotropin levels are higher than before or during the therapy. The LH release after GnRH stimulation shows the same trend.     

Prolactin response after gonadotropin-releasing hormone in the polycystic ovary syndrome

The administration of gonadotropin-releasing hormone (GnRH) has been shown to stimulate prolactin (PRL) release under certain conditions. The authors compared PRL responses after GnRH in normoprolactinemic patients with the polycystic ovary syndrome (PCO) with those of normal ovulatory women in the follicular phase. Seven of 15 patients had a significant increase in PRL after GnRH, whereas none of the control subjects had a positive response. After 1 week of oral L-dopa, the responders no longer exhibited this positive response. Baseline PRL levels in responding patients with PCO were similar to levels in control subjects, whereas nonresponding patients with PCO had higher PRL levels. Baseline follicle-stimulating hormone (FSH)/luteinizing hormone (LH) ratios were higher in patients with a positive response. The positive PRL response after GnRH was not correlated with baseline serum LH, the LH/FSH ratio, delta maximum LH responses, serum testosterone (T), unbound T, or baseline PRL. The positive response correlated positively with serum levels of unbound estradiol (P less than 0.05) and serum unbound estradiol/unbound T ratios (P less than 0.01). These data suggest that under certain conditions a subgroup of patients with PCO may demonstrate a positive PRL response after GnRH. Dopamine, gonadotropins, and estrogen may play a role in this interaction.     

The response to gonadotropin-releasing hormone in hirsutism after treatment with cyproterone acetate

The authors studied the response of the luteinizing hormone (LH), follicle-stimulating hormone (FSH), proclatin (PRL) and testosterone (T) to the intravenous injection of 100 microgram of synthetic gonadotropin-releasing hormone (GnRH) in hirsute women in the follicular phase, prior to and after the administration of cyproterone acetate (CPA). The GnRH stimulation before and after the CPA therapy induced a significant increase in plasma LH and FSH levels (P less than 0.01) and a significant drop in the plasma PRL concentration (p less than 0.05). Unchanged plasma T levels were observed during the test, prior to the CPA administration. Following the CPA application there was a significant increment of basal plasma PRL levels (p less than 0.05) and a significant drop of plasma FSH levels (p less than 0.01). No significant changes were observed, however, in LH and T levels. During the GnRH stimulation, after the administration of CPA, a significant decrease in T levels was noted (p less than 0.01). Considering basal concentrations of the hormones studied and the response to the LHR stimulation test, CPA was found to have no beneficial effect on the hypothalamic-pituitary dysfunction typical of androgenization in females.